Categories: cell biology, immunology, physiology
BACKGROUND
Skin aging is a biological process characterized by architectural and functional alterations that promote reduced wound healing capacity and compromised protective role against external pathogens [1]. Many different types of cells compose the skin niche (Figure 1), which confers this tissue with a number of functions, including maintaining body temperature, gathering sensory information from the environment and as a protective barrier [2].
Figure 1: The human skin niche and the residing cell types. Dermis and epidermis are two of the main skin layers. On one hand, the dermis contains different immune cell types, as well as fibroblasts and endothelial cells. On the other hand, the epidermis contains melanocytes, keratinocytes at different differentiation states and Langerhans cells, a unique population of tissue-residing macrophages. From Nestle FO., et al., 2009.
Given the high complexity of the skin architecture, synergic malfunctioning of the different cell populations results in its age-associated frailty. Furthermore, chronic inflammation has been widely demonstrated to modulate a diversity of processes underlying aging in different tissues [3], including the skin. Nonetheless, there is lack of evidence on the types of skin immune cells responsible for the pro-inflammatory environment associated to aging, and on the identity of the inflammatory cytokines that play a role.
To address this knowledge gap and using transcriptomics at the single-cell level, Paloma Solá and colleagues decipher the major transcriptional changes of different cell populations residing in the skin that take place during aging and they identify one of the key players driving skin aging.
KEY FINDINGS
In this study, the authors performed single-cell RNA-sequencing (scRNA-seq) of the different skin cell populations from adult and aged mice (17 to 25-, and 80 to 90-weeks of age, respectively). For this, the authors combined dermis or epidermis cell isolation and sorting, with RNA extraction and sequencing. It is worth noting that this process was performed in the dark period, to coincide with the active phases of mice.
By using this approach, transcription profiles linked to defective functions and increased inflammation were observed in both non-immune and immune dermal cells of aged mice. Among the former, Schwann cells appeared to be less efficient in their regenerative functions in skin, whereas endothelial cells and fibroblasts showed a shift towards a more pro-inflammatory state. Among the latter, dermal myeloid cells, T cells and innate lymphoid cells (ILCs) presented a remarkable upregulation of genes involved in different pro-inflammatory signaling pathways. Importantly, the authors noticed that in the case of specific T cell subsets and ILCs, these genes were predominantly related to the pro-inflammatory cytokine interleukin 17 (IL-17).
To address the physiological contribution of IL-17 signaling to skin aging, the authors treated aged mice (73-weeks-old) with IL-17 neutralizing antibodies for 12 weeks. They then assessed the transcriptomics of skin cells at single-cell level, as well as physiological parameters, such as the thickness of the cornified layer and the whole epidermal layer, as well as hair growth. First, the authors observed that IL-17 neutralization ameliorated the pro-inflammatory transcriptional state of dermal cells. Strikingly, the predominant anti-inflammatory effects were observed in non-immune dermal cells (fibroblasts, endothelial cells and Schwann cells). This is an interesting observation, since it suggests that non-immune dermal cells are most sensitive to anti-inflammatory treatments. Furthermore, assessment of the transcriptomics of epidermal cells upon IL-17 blockade also showed a restoration in the expression levels of pro-inflammatory cytokines. Importantly, reduction of other known epidermal aging traits was also observed, including pathways involved in oxidative stress functions and wound healing, highlighting the relevance of IL-17 in the development of age-associated traits in the skin. Lastly, aged mice treated with IL-17 neutralizing antibodies exhibited increased epidermal thickness and decreased cornified layer thickness compared to their adult counterparts, along with an improvement of the capacity of hair follicle growth upon epilation. This suggests that IL-17 blockade in aged mice improves epidermal health, thus pinpointing the physiological relevance of IL-17 skin aging.
WHY I CHOSE THIS PREPRINT
In their preprint, Paloma Solá and colleagues provide a very comprehensive and detailed characterization on the types of skin cell populations that present altered transcriptomics associated to aging. Besides, their approach allowed them to identify that upregulated IL-17 in specific lymphoid cell subsets acts as the driver of the pro-inflammatory state associated to skin aging. In my opinion, the authors elegantly provide valuable and complex data in a very easy-to-follow manner, making evident the real impact of their study. In fact, Paloma Solá and colleagues not only reveal a potential treatment to prevent unhealthy skin aging, but they also open the possibility to identify the exact molecular pathways that promote physiological skin aging.
MY QUESTIONS TO THE AUTHORS
- According to your data, there is a number of pro-inflammatory cytokines that show upregulated expression levels in different skin cell types of aged mice, including IL-6, IL-2, NFkB, and the STAT or TNF signaling pathways. Why did you focus on IL-17 signaling?
- If you performed a proof-of-concept experiment by providing adult mice with IL-17 in their skin, would you expect them to show accelerated skin aging?
- Considering your data on the anti-inflammatory effect that IL-17 blockade exerts in the skin niche, what is your speculation on the triggers of IL-17 upregulation in immune skin cells of aged mice?
- Does the IL-17 signaling from immune skin cells become systemic during aging? Could it be that IL-17 from other inflamed tissues is promoting its own regulation in the skin niche?
- Could enhanced IL-17 signaling be considered as a hallmark of autoimmune diseases?
REFERENCES
[1] López-Otín C., et al., The Hallmarks of Aging. Cell, 2013. doi: 10.1016/j.cell.2013.05.039
[2] Nestle FO., et al., Skin immune sentinels in health and disease. Nat Rev Immunol, 2009. doi: 10.1038/nri2622
[3] Ferrucci L and Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol, 2018. doi: 10.1038/s41569-018-0064-2
doi: https://doi.org/10.1242/prelights.31511
Read preprint
(No Ratings Yet)Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Felipe Del Valle Batalla
Also in the immunology category:
Alzheimer’s Disease Patient Brain Extracts Induce Multiple Pathologies in Vascularized Neuroimmune Organoids for Disease Modeling and Drug Discovery
Manuel Lessi
Global coordination of protrusive forces in migrating immune cells
yohalie kalukula
Integrin conformation-dependent neutrophil slowing obstructs the capillaries of the pre-metastatic lung in a model of breast cancer
Simon Cleary
Also in the physiology category:
Investigating Mechanically Activated Currents from Trigeminal Neurons of Non-Human Primates
Vanessa Ehlers
Geometric analysis of airway trees shows that lung anatomy evolved to enable explosive ventilation and prevent barotrauma in cetaceans
Sarah Young-Veenstra
Precision Farming in Aquaculture: Use of a non-invasive, AI-powered real-time automated behavioural monitoring approach to predict gill health and improve welfare in Atlantic salmon (Salmo salar) aquaculture farms
Jasmine Talevi
preLists in the cell biology category:
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
| List by | Felipe Del Valle Batalla et al. |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
| List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
| List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |
Also in the immunology category:
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
| List by | Alex Eve |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
| List by | Zhang-He Goh |
Zebrafish immunology
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
| List by | Shikha Nayar |
Also in the physiology category:
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |